The essay discusses isatin and its derivatives, highlighting their synthesis, reactivity, and biological evaluations. Various synthesis methods such as Sandmeyer, Martinet, Stolle, and Gassman are detailed, along with the biological activities of different isatin derivatives, notably their anti-cancer properties. Additionally, industrial applications of isatin, including its use as a corrosion inhibitor and in dye production, are also addressed, emphasizing its significance in synthetic and medicinal chemistry.

1. AN ESSAY ON
SYNTHESIS , REACTIVITY AND BIOLOGICAL
EVALUATION OF ISATIN AND IT’S DERIVATIVES
Produced by
Mahmoud Mohamed Abd El Samea Mohamed
Under supervisor
Prof.Dr : Fawzia zakaria El Ablack

2. INTRODUCTION
ISATIN (1H-INDOLE-2,3-DIONE), ALSO KNOWN AS INDENEDIONE AND INDOLE QUINONE, IS ONE SUCH
BIOLOGICALLY ACTIVE HETEROCYCLIC MOIETY. IT HAS A NITROGEN ATOM AT POSITION 1 AND TWO
CARBONYL GROUPS AT POSITIONS 2 AND 3 (FIG. 1) IN THIS REVIEW, WE HAVE SUMMARIZED THE
MOST RECENT LITERATURE FOR THE SYNTHESIS, CHEMISTRY, BIOLOGICAL AND INDUSTRIAL
APPLICATIONS OF ISATIN AND ITS DERIVATIVES.

3. SYNTHESIS OF ISATIN DERIVATIVES
• The Sandmeyer synthesis is one of the oldest method , This method has some economic
advantages, as the reagents are cheap and readily available, and the yields are usually high .
• Martinet isatin synthesis
• Stolle method : The most important alternative to Sandmeyer synthesis In this method anilines
are reacted with oxalyl chloride to form an intermediate chlorooxalylanilide which can be
cyclized in the presence of a Lewis acid, usually aluminium chloride to give the corresponding
isatin.
• Gassman method : This method involves the formation and subsequent oxidation of an
intermediate 3-methylthio-2-oxindole to give the corresponding substituted isatins .

4. Isatin derivatives
Fig. 2 shows the substitution of the aryl ring (A), alkylation of the nitrogen atom in the moiety (B) and also
modifications at its C2 and/or C3 carbonyl functionalities, which lead to the formation of a number of
biologically important derivatives.

5. bromo derivatives are found
to exhibit anti-cancer activity
against the human lymphoma
cell line
C-5-substituted isatin
derivatives:is an important
scaffold in the designing of
effective anti-cancer drugs
whereas substitution with the
methoxy group at C-5 results in
effective carbonic anhydrase
inhibitors
C3-Substituted isatin derivatives
moiety is an important
constituent of many
pharmaceutically essential
compounds such as sunitinib
and hesperidin
C-2-substitutedThese are
present as important
fragments in various
biologically active
moleculessuchas(+)austamid
e,
cephalinone
N-Substituted isatin
derivatives show many
biological applications.
They are effective
inhibitors of carbonic
anhydrase isoform IX
Spiro derivatives have been
found to show prominent
pharmacological activity,
especially in the chemistry of
natural products.
1-methylisoindigo1-Methylisoindigo, or
meisoindigo, is a well-known indirubin
derivative known for its activity against various
forms of leukemia, such as chronic
myelogenous leukemia (CML)

6. Structural characteristics
Tautomerization Spectral studies
• The UV-visible spectrum of isatin shows an
absorption maximum in the region of 260 nm to
350 nm corresponding to a π → π* transition due
to the aromatic ring,
• the IR spectrum of isatin shows two strong bands
at 1740 and 1620 cm−1, representing the carbonyl
stretching vibrations. A broad band accompanied
by some sub-bands occurs at 3188
cm−1 corresponding to N–H stretching
The 1H-NMR spectrum of isatin
shows a doublet at δ 7.47 ppm and 6.86 ppm corresponding
to Hb and He respectively. The hydrogen atom (Ha) attached
to nitrogen appears as a singlet at approximately δ 11.03
ppm. The protons Hc and Hd show triplets at δ 7.05 ppm and
7.57 ppm, respectively.
isatin exists as two tautomeric forms, lactam (1) and
lactim (2), in which a proton transfer between the
nitrogen atom and the oxygen atom present at the
second carbon occurs.37 In the solid state, isatin
predominantly exists in the lactam structure.

7. Reactions of isatin
Friedel–Crafts reactions
Friedel–Crafts reactions are an important class of
organic syntheses used to form highly functionalized
aromatic compounds, which can in turn generate
important pharmaceutically relevant compounds
Oxidation
Isatoic anhydride (8), an abundantly employed
compound in herbicide production and in medicinal
chemistry, has been obtained through the oxidation
of isatin

8. Aldol reactions
Aldol reactions produce β-hydroxyl carbonyl compounds,
which serve as important intermediates in the synthesis of
biologically active derivatives
Alleno-aldol condensation of isatins with allenic esters to give
carbinol allenoates.
Miscellaneous reactions
Alkylation of isatin is a synthetically viable reaction
that uses an alkylating agent, generally an alkyl or
aryl halide, in the presence of

9. Biological applications of isatin:
• The anti-cancer activity of isatin
• Isatins as histone deacetylase (HDAC) inhibitors
Anti-bacterial activity

10. Industrial applications
Isatin as a corrosion inhibitor: Isatin derivatives and their Mannich bases have been reported as
efficient inhibitors against aluminum and steel corrosion.
Fluorescent sensor/probe
Detection and quantification of metal ions in biological systems and in the
environment. . Recently, isatin functionalized nanoporous SBA-15 has been
reported as a selective fluorescent probe for the detection of HgIJII) in wate.
Dyes:
Dyes are widely used as coloring agents in the cotton and textile industries and also play an important role in
modern electronics. Isatin and its derivatives like indigo (C-2-substituted derivative) and isoindigo (C-3-
substituted derivative) are versatile natural dyes. Indigo, probably the oldest and the most famous dye, has
been used in the textile industry as a vat dye.
indigo Isoindigo

11. Miscellaneous applications ‫متنوعة‬ ‫تطبيقات‬ -
• Isatins and derivatives have been used in the development of colour photographic
recording materials,
• of blood coagulation promoters.
• of liquid crystal components for display devices and in the inhibition of corrosion of
aluminum and Fe-Ni alloys and of iron.
• Isatin can be used as a photosensitizer, together with a photo initiator, for Methacrylate
and epoxy silicone polymerization.
• also used for the synthesis of branched polycarbonate resins, improving the moldability of
this polyme
• Organic analytical chemistry: Isatin is known to be a colour reagent for the amino acid proline,
forming a blue derivative.

12. Conclusions
• Isatins continue to be one of the most researched areas in synthetic and
medicinal chemistry. Owing to the medicinal use associated with isatin
derivatives.
• the chemical reactions shown by isatins are also very crucial, since these
reactions in turn produce derivatives such as 2-quinolones, isatoic anhydride,
and 2-oxindoles, which are biologically potent ‫قوية‬.
All thanks and appreciation to my honorable
professors for the good listening and giving
me the opportunity
Mahmoud el manyalawy